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干性的二十年:从干细胞到转录亢进再回归

20 years of stemness: From stem cells to hypertranscription and back.

作者信息

Kim Yun-Kyo, Ramalho-Santos Miguel

机构信息

Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto ON M5G 1X5, Canada.

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto ON M5T 3L9, Canada; Department of Molecular Genetics, University of Toronto, Toronto ON M5G 1X5, Canada.

出版信息

Stem Cell Reports. 2025 Mar 11;20(3):102406. doi: 10.1016/j.stemcr.2025.102406. Epub 2025 Feb 6.

DOI:10.1016/j.stemcr.2025.102406
PMID:39919752
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11960510/
Abstract

Transcriptional profiling of stem cells came of age at the beginning of the century with the use of microarrays to analyze cell populations in bulk. Since then, stem cell transcriptomics has become increasingly sophisticated, notably with the recent widespread use of single-cell RNA sequencing. Here, we provide a perspective on how an early signature of genes upregulated in embryonic and adult stem cells, identified using microarrays over 20 years ago, serendipitously led to the recent discovery that stem/progenitor cells across organs are in a state of hypertranscription, a global elevation of the transcriptome. Looking back, we find that the 2002 stemness signature is a robust marker of stem cell hypertranscription, even though it was developed well before it was known what hypertranscription meant or how to detect it. We anticipate that studies of stem cell hypertranscription will be rich in novel insights in physiological and disease contexts for years to come.

摘要

本世纪初,随着利用微阵列技术对细胞群体进行整体分析,干细胞转录谱分析应运而生。从那时起,干细胞转录组学变得越来越复杂,特别是随着近年来单细胞RNA测序的广泛应用。在此,我们探讨了一个现象:20多年前通过微阵列技术鉴定出的胚胎干细胞和成体干细胞中上调基因的早期特征,意外地促成了近期一项发现,即跨器官的干/祖细胞处于转录亢进状态,也就是转录组的整体升高。回顾过去,我们发现2002年的干性特征是干细胞转录亢进的一个可靠标志物,尽管它是在人们还不知道转录亢进是什么意思或者如何检测它之前就开发出来的。我们预计,在未来几年里,对干细胞转录亢进的研究将在生理和疾病背景方面带来丰富的新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af6e/11960510/117082be6d92/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af6e/11960510/c775313e926c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af6e/11960510/117082be6d92/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af6e/11960510/c775313e926c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af6e/11960510/117082be6d92/gr2.jpg

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本文引用的文献

1
Hypertranscription: the invisible hand in stem cell biology.转录亢进:干细胞生物学中的无形之手。
Trends Genet. 2024 Dec;40(12):1032-1046. doi: 10.1016/j.tig.2024.08.005. Epub 2024 Sep 12.
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Origins of cancer: ain't it just mature cells misbehaving?癌症的起源:难道不就是成熟细胞的行为异常吗?
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Ageing-associated changes in transcriptional elongation influence longevity.与衰老相关的转录延伸变化影响寿命。
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Absolute scaling of single-cell transcriptomes identifies pervasive hypertranscription in adult stem and progenitor cells.单细胞转录组的绝对定量分析鉴定出成年干细胞和祖细胞中广泛存在的过转录现象。
Cell Rep. 2023 Jan 31;42(1):111978. doi: 10.1016/j.celrep.2022.111978. Epub 2023 Jan 11.
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Global genome decompaction leads to stochastic activation of gene expression as a first step toward fate commitment in human hematopoietic cells.全球基因组解压缩导致人类造血细胞命运决定的第一步是基因表达的随机激活。
PLoS Biol. 2022 Oct 26;20(10):e3001849. doi: 10.1371/journal.pbio.3001849. eCollection 2022 Oct.
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Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression.在 15 种癌症类型中,肿瘤细胞总 mRNA 表达的估计可预测疾病进展。
Nat Biotechnol. 2022 Nov;40(11):1624-1633. doi: 10.1038/s41587-022-01342-x. Epub 2022 Jun 13.
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Transposable element sequence fragments incorporated into coding and noncoding transcripts modulate the transcriptome of human pluripotent stem cells.可转座元件序列片段整合到编码和非编码转录本中,调节人类多能干细胞的转录组。
Nucleic Acids Res. 2021 Sep 20;49(16):9132-9153. doi: 10.1093/nar/gkab710.
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Chd1 protects genome integrity at promoters to sustain hypertranscription in embryonic stem cells.Chd1 保护启动子处的基因组完整性以维持胚胎干细胞的过度转录。
Nat Commun. 2021 Aug 11;12(1):4859. doi: 10.1038/s41467-021-25088-3.
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Hypertranscription and replication stress in cancer.癌症中的转录亢进与复制应激
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